| Project/Area Number |
12670324
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Saga Medical School |
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Principal Investigator |
ICHIBA Masayoshi School of Medicine, Associate professor, 医学部, 助教授 (60184628)
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| Co-Investigator(Kenkyū-buntansha) |
TOMOKUNI Katsumaro School of Medicine, Professor, 医学部, 教授 (40032891)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | DNA adduct / Repair / バイオマーカー / メトル化 / リンパ球 |
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| Research Abstract |
Environmental carcinogens are enzymatically activated to form intermediates that can react with cellular DNA and form DNA adducts. The measurement of DNA adducts is a useful indicator for environmental carcinogen exposure monitoring. DNA repair system was thought to be an important factor for DNA adduct levels. Because bulky aromatic DNA adducts were repaired by the nucleotide excision repair system. Excision repair has been mainly studied in Xeroderma pigmentosum and repair rate was shown to have very large inter-individual variation. But there have been few studies which have analyzed the effect of repair system on DNA adducts levels in healthy human samples.
DNA repair polymorphism may alter the structure of the DNA repair enzymes and modulate DNA adduct levels. We explored the relationship between polymorphism in the DNA excision repair enzyme XPD and DNA adduct levels in lymphocytes. We found that subjects with the XPD ex23 AC genotype showed significantly lower adduct levels than those with AA genotype.
Another viewpoint of evaluating the effect of repair enzyme on DNA adduct levels is the measurement of repair gene mRNA expression. We measured mRNA levels of repair enzyme ERCCI and XI'CC and compared with their DNA adduct levels. The DNA adduct levels showed a positive correlation with ERCC1 and a negative correlation with XPCC mRNA
Further studies are needed to characterize the role of DNA repair system and to estimate whether it affects the levels of other biomarkers on DNA damage
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